{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:46:24Z","timestamp":1792511184165,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T00:00:00Z","timestamp":1642809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/02233"],"award-info":[{"award-number":["PI17\/02233"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The hepatitis delta virus (HDV) genome has an autocatalytic region called the ribozyme, which is essential for viral replication. The aim of this study was to use next-generation sequencing (NGS) to analyze the ribozyme quasispecies (QS) in order to study its evolution and identify highly conserved regions potentially suitable for a gene-silencing strategy. HDV RNA was extracted from 2 longitudinal samples of chronic HDV patients and the ribozyme (nucleotide, nt 688\u2013771) was analyzed using NGS. QS conservation, variability and genetic distance were analyzed. Mutations were identified by aligning sequences with their specific genotype consensus. The main relevant mutations were tested in vitro. The ribozyme was conserved overall, with a hyper-conserved region between nt 715\u2013745. No difference in QS was observed over time. The most variable region was between nt 739\u2013769. Thirteen mutations were observed, with three showing a higher frequency: T23C, T69C and C64 deletion. This last strongly reduced HDV replication by more than 1 log in vitro. HDV Ribozyme QS was generally highly conserved and was maintained during follow-up. The most conserved portion may be a valuable target for a gene-silencing strategy. The presence of the C64 deletion may strongly impair viral replication, as it is a potential mechanism of viral persistence.<\/jats:p>","DOI":"10.3390\/v14020215","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T20:36:27Z","timestamp":1642970187000},"page":"215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Inspecting the Ribozyme Region of Hepatitis Delta Virus Genotype 1: Conservation and Variability"],"prefix":"10.3390","volume":"14","author":[{"given":"Beatriz","family":"Pacin-Ruiz","sequence":"first","affiliation":[{"name":"Liver Pathology Unit, Departments of Biochemistry and Microbiology, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4318-532X","authenticated-orcid":false,"given":"Mar\u00eda Francesca","family":"Cortese","sequence":"additional","affiliation":[{"name":"Liver Pathology Unit, Departments of Biochemistry and Microbiology, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1146-4084","authenticated-orcid":false,"given":"David","family":"Tabernero","sequence":"additional","affiliation":[{"name":"Liver Pathology Unit, Departments of Biochemistry and Microbiology, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas, Instituto de 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